Method of determining the severity of a lithogenesis condition and a composition of calculi forming salts

ABSTRACT

The present method for evaluating the extent of a lithogenesis process intensity and for determining the composition of lithogenic urate salts in urolithiasis resides in adding an aqueous protein solution to a urine sample in a ratio of 9:1, 7:1 or 5:1, respectively; applying the mixture thus-prepared as a drop onto a smooth surface for drying for at least 24 hours; determining the nature of crystallization of urate salts in the marginal zone of the urine sample, the presence of separate, singly occurring crystals, conglomerates of crystals and a complete crystallization of this marginal zone being indicative, respectively, of a weak, moderate or a highly pronounced extent of a lithogenesis process intensity; the composition of crystalline formations is determined, while, simultaneously, establishing the constitution of urate salts in the central zone of that same urine sample, followed by carrying out a comparative analysis to said two compositions to determine the composition of lithogenic urate salts.

FIELD OF THE INVENTION

The present invention relates to analytical methods for use in medicineand, more specifically, to a method for evaluating the extent of alithogenesis process intensity and for determining the composition oflithogenic urate salts in urolithiasis.

BACKGROUND OF THE INVENTION

The problems of investigating the dynamic aspects of a lithogenesisprocess in the human organism, of studying its intensity, of determiningthe salt composition in the course of a lithogenesis process arecurrently being researched. Knowledge in this field makes it possible toprevent the formation of urate calculi, to introduce timely correctionsinto the lithogenesis process, to prescribe and carry out individualtherapeutic treatment for urolithiasis cases.

Known in the prior art are methods for predicting urolithiasis basedupon detecting a lithogenesis process, such as, e.g. a prediction methodbased upon detection of urate salt crystals in freshly discharged urineor in urine analyzed Shortly after urination (Ref. V. Ye. Predtechensky"Guide for Clinical Laboratory Investigations", 1964 MedicinaPublishers, pp. 420-446), or a method for predicting urolithiasis (SU,A, 1 629 846) based upon evaluation of the crystal-forming activity ofurine by mixing solutions of calcium chloride, sodium oxalate and urine,followed by holding the resultant mixture and then counting the numberof crystals formed.

However, the above-cited methods are aimed only at detecting alithogenesis process, and they do not allow the determination to be madeas to the extent of this process intensity.

Equally known in the prior art is a method for predicting urolithiasis,in which it is recommended to evaluate the extent of risk of calciumphosphate crystallization in urine by counting the number of crystalsthus-formed and having a specific size using recommended mathematicalprocedures (refer, please, to the "Urological Research", No. 2, 15,1987, Springer-Verlag, H.-G. Tiselius, "Measurement of the Risk ofCalcium Phosphate Crystallization in Urine", pp. 79-81). The lattermethods calls for sophisticated mathematical calculations, and its onlypurpose is to detect the fact of a lithogenesis process.

Also known in the prior art is a method for predicting of urolithiasis(PCT/SU 91/00140), by preparing a protein solution, e.g. albuminsolution is added to a urine sample, the resultant mixture is subjectedto drying and, if a 100%-crystallization of the urine sample takesplace, a urolithiasis case is predicted. The latter method is also aimedat revealing a lithogenesis process, and it cannot be used forevaluating the extent of intensity of a lithogenesis process.

Moreover, there are known in the prior art methods for determining thecomposition of urate salts participating in urolithiasis (V. Ye.Predtechensky "Guide for Clinical Laboratory Investigations", 1964Medicina Publishers, Moscow, pp. 452-454; Wandt M., Underhill L. "Brit.J. Urol.", 1988 61 No. 6 478-481; Schubert G., Brien G., Adam K. "Z.Klin. Med.", 1989, 44, No. 11 , 923-928; Nichino T., Sakura T., Sato T.,Koiso K., Kaneko S. "Jap. J. Nephrol.", 1987, 29, No. 5, 571-575). Allof the above-cited methods are based upon study of the urineconstituents (salt deposit, sand, concretions) by the physico-chemicalroute using adsorption, ion exchange, such as, e.g. chromatography,using X-ray structural analysis, X-ray spectral analysis, thermalanalysis involving study of nuclear magnetic resonance, electronpara-magnetic resonance and other spin effects.

All of the above-cited methods are suitable only for study of alreadyformed calculi discharged from the human body, and they unable todetermine the chemical nature of nascent calculi at early urolithiasisstages, and that of calculi already fully formed, but not withdrawn fromthe body.

There exists in the prior art no method for determining the chemicalcomposition of calculi-forming urate salts at early urolithiasis stages,or for determining that of calculi fully formed, but not discharged fromthe organism.

DESCRIPTION OF THE INVENTION

The proposed method for evaluating the extent of intensity of alithogenesis process and for determining the composition ofcalculi-forming urates during urolithiasis is novel and has never beendescribed in the literature.

The present invention is aimed at developing a method which would makeit possible to evaluate --quickly and accurately--the extent ofintensity of lithogenesis process during urolithiasis process, as wellas to determine the salt composition of an urate calculus at any stageof its formation.

The above-formulated problem is solved owing to the followingimprovements introduced into the method for evaluating the intensity ofa lithogenesis process and for determining the composition of lithogenicurate salts in urolithiasis: into a urine sample an aqueous proteinsolution is added in a ratio of 9:1, 7:1 or 5:1, respectively; themixture thus-prepared is applied as a drop onto a smooth flat surface,followed by drying the drop for at least 24 hours; assessment is made ofthe nature of crystallization of urate salts in the marginal zone of theurine sample; if any individual crystals, crystalline conglomerates orin case of a complete crystallization of this marginal zone, judgementis made on a weak, moderate or a deeply pronounced extent of intensityof a lithogenesis process; the composition of these crystallineformations is determined, while, simultaneously, determining thecomposition of urate salts in the central zone of that same urinesample, followed by making a comparative analysis of these twocompositions for detecting the presence of lithogenic urate salts.

It is preferable that, as said aqueous protein solution, use be made ofan 8-12%-aqueous albumin solution. To improve the analysis accuracy,itis advisable that drying of a mixture drop applied onto a smooth surfacebe conducted at room temperature. In order to speed up and improveaccuracy of the analysis, it is preferable that X-ray spectrummicroanalysis be used for analyzing the elemental composition of saidcrystalline formations.

The method in accordance with the present invention has elicited thefollowing fact: there exists a relationship between the intensity of thecalculus formation process and the intensity of crystallization of uratesalts in the marginal zone of a urine sample. This phenomenon makes itpossible to rapidly and accurately determine in a urine sample theextent of the intensity of a lithogenesis process, thus providing apossibility to study the lithogenesis process in its dynamic aspects, tointroduce timely corrections into this process thereby preventing theformation of a urate calculus, and--if need be--to work out and followan individual therapeutic treatment course. Moreover, the method of thepresent invention makes it possible, well in advance of the actual factof the formation of a calculus in the human body, to determine thecomposition of calculi-forming urate salts and to take adequatepurposeful measures for removing these urate salts from the body and forpreventing their intake together with potable water and food stuffs. Thepresent analytical method makes it possible to learn, exactly whatcalculi-forming urate salts constitute the surface layer of a calculusduring a certain period of observation, if a calculus is detected in theurinary ways of a patient, since this information may be required, e.g.for lithotripsy.

A study of the composition of lithogenic urate salts in a dynamic aspect(including from the very moment of the onset of a calculus formationprocess) makes it possible to establish the composition and subsequentstructure of the entire calculus, which fact is important, iflithotripsy is envisaged.

Finally, the present method of analysis makes it possible to carry outeffective prophylaxis against urolithiasis recidives. The present methodis convenient, simple to carry out, and does not require any specialequipment.

PREFERRED EMBODIMENT OF THE INVENTION

As stated above, the present method for evaluating the extent ofintensity of a lithogenesis process is based upon the establishedrelationship between the degree of salt crystallization in the marginalzone of a urine sample and the calculus formation intensity. The presentmethod is carried out as follows:

Into a urine sample an aqueous protein solution (it is preferable thatan 8-12%-aqueous albumin solution be used ) is added in a ratio of 9:1,7:1 or 5: 1, respectively. For the purpose of analysis, it is possibleto use a urine sample taken in one of the above-specified ratios withthe aqueous albumin solution. For the sake of authenticity of ananalysis, it is possible to use two or three alternative ratios. Onedrop of a mixture thus--obtained is applied onto a flat surface,followed by drying for at least 24 hours at room temperature.

Once the drop is dried up, the intensity of urate salt crystallizationis assessed in the marginal zone of the urine sample: the presence ofseparate single crystals is indicative of a weak intensity of thecalculus formation process, the presence of conglomerates of saltcrystals--of a moderate intensity, and a complete crystallization ofthis marginal zone is indicative of a deeply pronounced intensity of acalculus formation process.

The absence of crystals in the marginal zone testifies to the fact thatno lithegenesis process takes place. The present method makes itpossible to achieve a two-pronged purpose, namely: to evaluate theextent of the process intensity and, at the same time, to determine thecomposition of lithogenic urate salts. Physical analytical methods(preferably X-ray spectrum microanalysis) are used to determine theelemental constitution of crystalline formations found in the marginalzone. At the same time, the elemental constitution of urate salts in thecentral zone of that same urine sample is determined, whereupon acomparative analysis of these two constitutions is conducted, on thebasis of which a conclusion is drawn on the chemical composition ofcalculus-forming urate salts. It should be borne in mind that a calculusformation process is a dynamic process, and, therefore, a saltconstitution may vary in time. The present method makes it possible todetermine the salt constitution of a calculus as it is formed or may beformed in the future with the given salt constitution of urine.

The method of the present invention has undergone tests in clinicallaboratories. To evaluate the extent of the intensity of thelithogenesis process, 12 patients belonging to the category of theso-called "calculus dischargers" (i, e. patients, in whom spontaneousdestruction and discharge of calculi is observed) and 128 practicallyhealthy persons in their pre-clinical urolithiasis stage, have beenexamined. The fact that these practically healthy persons are in theirpre-clinical urolithiasis stage has been established by the conventionalmethod, but the extent of the intensity of the lithogenesis processremained unknown. The following investigation procedure has been used: aurine sample was taken, an aqueous protein (albumin) solution was addedthereto in a ratio of 9:1, 7:1 or 5:1, respectively, the mixturethus-obtained was applied as a drop onto a microscopic slide, and driedat room temperature for 24 hours. Then, a study has been undertaken tofind, whether there are any crystals in the marginal zone of the driedurine sample. The study results are reported in Tables 1 and 2 thatfollow:

                  TABLE 1                                                         ______________________________________                                        The results of clinical and laboratory tests                                  on patients belonging to the category of                                      "calculi dischargers"                                                         ______________________________________                                                                Extent of                                                       Urine/aqueous albumin                                                                       lithogenesis                                                    solution ratio                                                                              process                                               Nos.  Patients  9:1     7:1   5:1   intensity                                 1     2         3       4     5     6                                         ______________________________________                                        1     Patient B.                                                                              +       -     -     weak                                      2     Patient L.                                                                              +       -     -     weak                                      3     Patient Ya.                                                                             +       -     -     weak                                      4     Patient Sh.                                                                             +++     ++    -     moderate                                  5     Patient M.                                                                              +++     ++    -     moderate                                  6     Patient R.                                                                              +++     ++    -     moderate                                  7     Patient O.                                                                              +++     ++    -     moderate                                  8     Patient K.                                                                              +++     ++    -     moderate                                  9     Patient S.                                                                              +++     ++    -     moderate                                  10    Patient U.                                                                              +++     ++    -     moderate                                  11    Patient A.                                                                              +++     +++   +++   well pronounced                           12    Patient D.                                                                              +++     +++   +++   well pronounced                           ______________________________________                                                         Time (months) of detection of                                                 calculus during subsequent clinical                          Nos.   Patients  examinations                                                 1      2         7                                                            ______________________________________                                        1      Patient B.                                                                              27 months                                                    2      Patient L.                                                                              24                                                           3      Patient Ya.                                                                             29                                                           4      Patient Sh.                                                                             7                                                            5      Patient M.                                                                              8                                                            6      Patient R.                                                                              8                                                            7      Patient O.                                                                               7 months                                                    8      Patient K.                                                                              9                                                            9      Patient S.                                                                              8                                                            10     Patient U.                                                                              7                                                            11     Patient A.                                                                              3                                                            12     Patient D.                                                                              2                                                            ______________________________________                                         Notes:                                                                        (+)  the presence of separate, singly occuring crystals in the marginal       zone of a urine sample.                                                       (++)  conglamerates of crystals.                                              (+++)  complete crystallization of the marginal zone.                    

                  TABLE 2                                                         ______________________________________                                        The results of clinical and laboratory tests on                               practically healthy persons in their preclinical                              urolithiasis stage                                                                                                  Time of                                                                       detection                                                              Extent of a cal-                                                              of li- culus                                        Number of                 thoge- during                                       persons                   nesis  next cli-                                    under     Urine/aqueous albumin                                                                         process                                                                              nical                                        exam-     solution ratio  inten- tests                                   Nos. ination   9:1     7:1   5:1   sity   (months)                            ______________________________________                                        1    61        +       -     -     weak   24-30                               2    49        +++     ++    -     mode-  7-8                                                                    rate                                       3    18        +++     +++   +++   well   2-3                                                                    pronoun-                                                                      ced                                        ______________________________________                                         Notes:                                                                        (+)  the presence of separate, singly occuring crystals in the marginal       zone of a urine sample.                                                       (++)  conglomerates of crystals.                                              (+++)  complete crystallization of the marginal zone.                    

As seen from the results reported in Tables 1 and 2, there is a100%-agreement between the laboratory and clinical test resultsindicative of the formation of a urate calculus. In one group of"calculi discharger" patients affected by a lithogenesis process with adeeply pronounced intensity (i.e. a group in which a completecrystallization of the marginal zone was observed), newly formed calculiwere detected upon expiration of some 2-3 months; in another groups ofpatients (those with a partial crystallization of the crystallineconglomerates in the marginal zone) affected by a lithogenesis processwith a moderate intensity extent, newly formed calculi were detectedupon expiration of some 7-8 months; and in third group of patientsaffected with a weakly pronounced lithogenesis process (i.e. separate,singly occurring crystals in the marginal zone), newly formed calculiwere found upon expiration of 2-2.5 years. The same is valid for theresults of clinical and laboratory tests on practically healthy personsaffected by urolithiasis in its pre-clinical stage (Table 2).Consequently, the method in accordance with the present invention makesit possible to draw a conclusion on the lithogenesis process intensity(i.e. to assess the extent of the process intensity) and to makejudgement on the time it takes to form a calculus.

Simultaneously with evaluation of the extent of the lithogenesis processintensity, studies of the composition of calculi-forming urate saltswere conducted in 13 patients affected with urolithiasis (with adefinitely established extent of the lithogenesis process). Out of these13 patients 6 patients belonged to the category of "calculidischargers", and 7 underwent lithotripsy. A urine sample was appliedonto a mecroscopic slide to dry up. A complete crystallization of themarginal zone was observed (which bespoke of a deeply pronouncedlithogenes is process). The phase or elemental composition of thesecrystalline formations was determined by the X-ray structure analysisand X-ray spectrum microanalysis. The results of these analyses of theelemental (phase) composition of crystalline formations occurring in themarginal zone of urine samples were compared with the results obtainedby analyzing the urate calculi actually released later.

As follows from the analytical results reported in Table 3, the resultsof an analysis of the composition of crystalline formations of themarginal zone of

                  TABLE 3                                                         ______________________________________                                        Comparative results of the analyses of salt                                   constitutions of crystalline formations occurring                             in the marginal zone of urine samples and of                                  actually discharged urate calculi                                             ______________________________________                                                                     Elemental (phase)                                                             constitution of                                                               salts in crystalline                                                          formations in                                                                 marginal zone of                                 Nos. Patients   Diagnosis    a urine sample                                   1    2          3            4                                                ______________________________________                                        1    Patient K. Urolithiasis Uric acid*                                       2    Patient P. Urolithiasis Uric acid. Acid urate                                                         of ammonium*                                     3    Patient H. Urolithiasis Uric acid. Acid urate                                                         of ammonium*                                     4    Patient L. Urolithiasis Uric acid*                                       5    Patient R. Urolithiasis. Se-                                                                          Calcium, phosphorus,                                             condary pyelo-                                                                             magnesium**                                                      nephritis                                                     6    Patient A. Urolithiasis. Se-                                                                          Calcium, phosphorus,                                             condary pyelo-                                                                             magnesium                                                        nephritis                                                     7    Patient N. Urolithiasis. Se-                                                                          Phosphorus, calcium,                                             condary pyelo-                                                                             zinc**                                                           nephritis                                                     8    Patient V. Urolithiasis. Se-                                                                          Phosphorus,                                                      condary pyelo-                                                                             calcium**                                                        nephritis                                                     9    Patient A. Urolithiasis Phosphorus, calcium,                                                          magnesium**                                      10   Patient I. "            Phosphorus, calcium**                            11   Patient G. Urolithiasis.                                                                              Calcium**                                                        Secondary pyelo-                                                              nephritis                                                     12   Patient T. Urolithiasis.                                                                              Calcium**                                                        Secondary pyelo-                                                              nephritis                                                     13   Patient A. Urolithiasis.                                                                              Calcium**                                                        Secondary pyelo-                                                              nephritis                                                     ______________________________________                                                              Composition of discharged                                                     urate calculi (prevailing                                                     in surface layer of a                                   Nos.      Patients    calculus)                                               1         2           5                                                       ______________________________________                                        1         Patient K.  Urates                                                  2         Patient P.  Urates                                                  3         Patient H.  Urates                                                  4         Patient L.  Urates                                                  5         Patient R.  Phosphates                                              6         Patient A.  Phosphates                                              7         Patient N.  Phosphates                                              8         Patient V.  Phosphates                                              9         Patient A.  Phosphates                                              10        Patient I.  Phosphates                                              11        Patient G.  Oxalates                                                12        Patient T.  Oxalates                                                13        Patient A.  Oxalates                                                ______________________________________                                         *the results of an Xray structure analysis.                                   **the results of an Xray spectrum microanalysis.                         

a urine sample are matched by the results of a study of the compositionof an actually discharged urate calculus.

Consequently, the method of the present invention makes it possible topredict or to determine the salt constitution of a calculus at thepre-clinical stages of development of urolithiasis, and this fact may beadvantageously used for prevention of the concrement formation.

For better understanding of the essence of the present invention, thefollowing specific embodiments of the present method are reported:

EXAMPLE 1

Patient B., 50 years old, was taken under observation by a clinicallaboratory for 2 years. After discharge of a calculus from his body, hewas taken under dynamic observation. His urine was investigated weeklyby the present method. The following procedure was used forinvestigations:

An aqueous albumin solution was added to his urine sample in a ratio of9:1, 7:1 or 5:1, respectively. The resultant mixture was applieddrop-wise onto a microscopic slide and dried up at room temperature for24 hours. The nature of salts crystallized in the marginal zone of theurine sample was next determined. During four months, there was observeda deeply pronounced extent of the calculus formation process intensity(i.e. a complete crystallization of the marginal zone of the urinesample was observed). Simultaneously, by means of an X-ray spectrummicroanalysis, the elemental constitution of crystalline formations inthe marginal zone was established. For a comparative analysis, theelemental constitution of the central zone of the same urine sample wasdetermined. There was established that a considerable excess in thecontents of some individual elements in the marginal zone over those inthe central zone becomes the basis for calculi-forming salts.

The results of determination of the composition of calculi-forming saltsare confirmed by the results of a calculus composition analysis afterthe calculus discharge from the body. The results of a study arereported in Table 4 below:

                  TABLE 4                                                         ______________________________________                                        The results of a comparative analysis of the                                  elemental constitutions of the central and                                    marginal zone of a urine sample and a discharged                              urate calculus                                                                ______________________________________                                        Material under                                                                            Elements, %%                                                      study       Na       Mg     P      S    Cl                                        1           2        3    4      5    6                                   ______________________________________                                        1.  Urine sample                                                                              27.4     1.1   3.4   1.1  62.6                                    (central zone)                                                            2.  Urine sample                                                                              17.3     0.9  14.6   9.5  39.6                                    (marginal zone)                                                           3.  Extracted urate                                                                           --       3.3  30.3   --   --                                      calculus                                                                  ______________________________________                                        Material under   Elements, %%                                                 study            K      Ca        Zn  Si                                             1             7      8       9   10                                    ______________________________________                                        1.     Urine sample   3.3   --      --  --                                           (central zone)                                                         2.     Urine sample  11.6    6.1    --  --                                           (marginal zone)                                                        3.     Extracted urate                                                                             --     64.2    --  --                                           calculus                                                               ______________________________________                                    

As follows from Table 4, calcium and phosphorus are the mainconstituents of calculi-forming salts, and this inference is confirmedby the constitution of the calculus after its extraction from thepatient's body.

After removal of the calculus from the body, a medical treatment coursewas prescribed to the patient and his urine was examined weekly for twomore years. The results of dynamic observation (i.e. the results ofperiodically evaluating the extent of the lighogenesis processintensity) of the patient in question are reported in Table 5 below:

                  TABLE 5                                                         ______________________________________                                        The results of observing the extent of the                                    lithogenesis process intensity in patient B. as                               viewed dynamically from the very beginning of                                 the treatment course                                                                    Crystallization degree of the                                                                     Extent                                                    marginal zone of a urine sample                                                                   of the                                                    at a urine/aqueous albumin                                                                        lithogenesis                                    Examination                                                                             solution ratio of   process                                         periodicity                                                                             9:1       7:1      5:1    intensity                                 1         2         3        4      5                                         ______________________________________                                        1 week    ++        ++       -      moderate                                  1 month   +         +        -      weak                                      2-4 months                                                                              -         -        -      no process                                5-7 months                                                                              ++        +        -      moderate                                  8 months  +         -        -      weak                                      9-13 months                                                                             -         -        -      no process                                14 months +         -        -      weak                                      15-20 months                                                                            +         -        -      weak                                      ______________________________________                                         Note:                                                                         + the presence of separate, singly occurring crystals.                        ++ conglomerates of crystals.                                                 - no crystals are observed.                                              

EXAMPLE 2

The extent of the lithogenesis process intensity in a urine sample ofthe patient H. was evaluated using the procedure described in Example 1.It was established that the patient H. was affected with a deeplypronounced lithogenesis intensity (i.e. a complete crystallization ofthe marginal zone of the urine sample was observed). By means of anX-ray spectrum microanalysis, the elemental constitution of crystallineformations in the marginal zone was determined. For the sake ofcomparison, a comparative analysis was conducted of the elementalconstitutions of the marginal and central zones of a dried urine sample.The results thus-obtained of determining the constitution of lithogenicsalts were confirmed by an analysis of the composition of the uratecalculus after its extraction from the patient's body. The analyticalresults are reported in Table 6.

As seen from the data of Table 6, it is mainly calcium that is the maincalculus-forming element, and this conclusion is confirmed by the factthat the calcium content in the calculus is 93%.

                  TABLE 6                                                         ______________________________________                                        The results of a comparative analysis of the                                  elemental constitutions of the central and                                    marginal zones of a urine sample and of an                                    extracted urate calculus                                                      ______________________________________                                        Material under                                                                            Elements, %%                                                      study       Na       Mg     P      S    Cl                                        1           2        3    4      5    6                                   ______________________________________                                        1.  Urine sample                                                                              26.2     2.0  15.1   8.9  30.5                                    (central zone)                                                            2.  Urine sample                                                                              27.6     2.1  19.6   12.3 26.0                                    (marginal                                                                     zone)                                                                     3.  Extracted    1.5     --    4.1   0.5  --                                      urate calcu-                                                                  lus                                                                       ______________________________________                                        Material under Elements, %%                                                   study          K      Ca         Zn   Si                                            1            7      8        9    10                                    ______________________________________                                        1.    Urine sample 13.0   2.6      --   --                                          (central zone)                                                          2.    Urine sample  4.8   7.6      --   --                                          (marginal zone)                                                         3.    Extracted ura-                                                                             --     93.0     --   --                                          te calculus                                                             ______________________________________                                    

EXAMPLE 3

The extent of the lithogenesis process intensity in a urine sample ofthe patient K. was evaluated using the procedure described in Example 1.It was established that the patient K. was affected with a deeplypronounced lithogenesis intensity (i.e. a complete crystallization ofthe marginal zone in his urine sample was observed). By means of anX-ray spectrum microanalysis, the elemental constitution of crystallineformations in the marginal zone was determined. A comparative analysiswas conducted of the elemental constitutions of the marginal and centralzones of a dried urine sample. The results of determination of thecomposition if calculi-forming salts were confirmed by the actualcomposition of a calculus after its extraction from the patient's body.The analytical results are reported in Table 7 below:

                  TABLE 7                                                         ______________________________________                                        The results of a comparative analysis of the                                  elemental constitutions of the central and                                    marginal zones of a urine sample and of an                                    extracted urate calculus                                                      ______________________________________                                        Material under                                                                             Elements, %%                                                     study        Na      Mg      P     S     Cl                                       1            2       3     4     5     6                                  ______________________________________                                        1.  Urine sample 17.2    --    15.8  12.2  31.1                                   (central zone)                                                            2.  Urine sample 12.7     3.9  23.3   9.2  22.4                                   (marginal zone)                                                           3.  Extracted    --      14.0  39.3  --    --                                     urate calculas                                                            ______________________________________                                        Material under Elements, %%                                                   study          K      Ca        Zn   Si                                             1            7      8       9    10                                     ______________________________________                                        1.    Urine sample 19.7   2.6     --   --                                           (central zone)                                                          2.    Urine sample 12.5   5.5     --   --                                           (marginal zone)                                                         3.    Retracted    --     44.7    --   --                                           urate calculus                                                          ______________________________________                                    

As follows from Table 7, calcium, phosphorus and magnesium are the mainconstituents of calculi-forming salts, and this conclusion is confirmedby the actual composition of the calculus after its extraction: Ca44.7%, P 39.3%, Mg 14.0%.

EXAMPLE 4

The extent of the lithogenesis process intensity in a urine sample takenfrom the patient S. was evaluated using the procedure described inExample 1. It was established that the patient S. was affected with ahighly intensive lithogenesis process (i.e. a complete crystallizationof the marginal zone in his urine sample was observed). By means of anX-ray spectrum microanalysis, the elemental constitution of crystallineformations in the marginal zone was determined. A comparative analysiswas conducted of the elemental constitutions of the marginal and centralzones of a dried urine sample. After establishing the fact that thepatient S. was affected with a highly intensive lithogenesis process anddetermining the composition of the calculi-forming salts, the patient S.underwent an individual therapy course. His urine sample was againsubjected to an analysis. The result thus-obtained are reported in Table8 below:

                  TABLE 8                                                         ______________________________________                                        The results of a comparative analysis of the                                  elemental constitutions of the central and                                    marginal zones of a urine sample and of an                                    extracted urate calculus (%%)                                                 ______________________________________                                                  Lithogenesis                                                                             Material                                                 Examination                                                                             intensity  under     Elements, %%                                   period    extent     study     Na   Mg    P                                   1         2          3         4    5     6                                   ______________________________________                                        Before    Highly pro-                                                                              Urine                                                    treatment nounced    sample                                                                        (centr.   25.2 1.5    7.1                                                     zone)                                                                         (marg.    14.1 0.2   14.6                                                     zone)                                                    After     No process (central  33.4 1.0   10.6                                treatment            zone)                                                                         (marg.    34.6 --    10.6                                                     zone)                                                    ______________________________________                                                  Lithogenesis                                                                             Material                                                 Examination                                                                             intensity  under     Elements, %%                                   period    extent     study     S    Cl    K                                   1         2          3         7    8     9                                   ______________________________________                                        Before    Highly pro-                                                                              Urine                                                    treatment nounced    sample                                                                        (central  7.8  37.1  16.4                                                     zone)                                                                         (marg.    2.7  17.0  8.4                                                      zone)                                                    After     No process (central  10.1 35.9  7.1                                 treatment            zone)                                                                         (marg.    8.3  35.9  6.4                                                      zone)                                                    ______________________________________                                                  Lithogenesis                                                                             Material                                                 Examination                                                                             intensity  under     Elements, %%                                   period    extent     study     Ca   Zn    Si                                  1         2          3         10   11    12                                  ______________________________________                                        Before    Highly     Urine                                                    treatment pronounced sample                                                                        (central  1.7  0.2   --                                                       zone)                                                                         (marg.    4.7  0.2   --                                                       zone)                                                    After     No process (central  1.4  1.3   --                                  treatment            zone)                                                                         (marg.    0.4  1.1   --                                                       zone)                                                    ______________________________________                                    

As follows from Table 8, calcium and phosphorus were the mainconstituents of calculi-forming salts (before treatment), whereas aftertreatment the lithogenesis process was altogether discontinued.

Industrial Applicabillty

The method of the present invention may be applicable in clinical andscientific laboratory research for analysis of the extent oflithogenesis process intensity, for carrying out studies of the dynamicaspects of lithogenesis processes, for determining the salt compositionof calculi at early urolithiasis stages, for preventing urate calculiformation and for prescribing an individual therapy course inurolithiasis cases.

What is claimed is:
 1. A method of determining the severity of a lithogenesis condition and a composition of calculi forming salts in a urine sample comprising mixing a urine sample with an aqueous protein solution to form a mixture having a urine to protein solution ratio of 9:1, 7:1 or 5:1, applying a drop of said mixture to a smooth surface, drying the drop for at least 24 hours, determining the extent of salt crystallization in a peripheral zone of the dried sample mixture, classifying the presence of singly occurring crystals, crystal conglomerates or complete crystallization respectfully as indicative of a weak, moderate or severe lithogenesis condition, determining a salt composition for the crystals in the peripheral zone and a central zone of the dried sample and determining the composition of the calculi forming salts in the urine sample through a comparative analysis of the salt compositions of the two zones of the dried sample mixture.
 2. A method as claimed in claim 1 wherein said aqueous protein solution is an 8-12% aqueous albumin solution.
 3. A method as claimed in claim 2 wherein X-ray spectrum microanalysis is used to determine the crystalline formations.
 4. A method as claimed in claim 1 wherein the drying of said drop of the mixture produced by mixing a urine sample with an aqueous protein solution is carried out at room temperature.
 5. A method as claimed in claim 4 wherein X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 6. A method as claimed in claim 1 wherein X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 7. A method of determining the severity of a lithogenesis condition and a composition of calculi forming salts in a urine sample comprising mixing a urine sample with an aqueous protein solution to form mixtures having a urine to protein solution ratio of 9:1, 7:1 and 5:1, applying a drop of each mixture to a smooth surface, drying the drops for at least 24 hours, determining the extent of salt crystallization in a peripheral zone of the dried sample mixtures, classifying the presence of singly occurring crystals, crystal conglomerates or complete crystallization respectfully as indicative of a weak, moderate or severe lithogenesis condition, determining a salt composition for the crystals in the peripheral zone and a central zone of the dried sample mixtures and determining the compositions of the calculi forming salts in the urine sample through a comparative analysis of the salt compositions of the two zones of the dried sample mixtures.
 8. A method as claimed in claim 7 wherein said aqueous protein solution is an 8-12% aqueous albumin solution.
 9. A method as claimed in claim 8 wherein the X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 10. A method as claimed in claim 7 wherein the drying of said drops of the mixtures produced by mixing a urine sample with an aqueous protein solution is carried out at room temperature.
 11. A method as claimed in claim 10 wherein the X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 12. A method as claimed in claim 7 wherein X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 13. A method of determining the severity of a lithogenesis condition and a composition of calculi forming salts in a urine sample comprising mixing a urine sample with an aqueous protein solution to form at least two mixtures; each of said mixtures having a urine to protein solution ratio of 9:1, 7:1 or 5:1 the ratio of urine to protein solution in each of said mixtures being different; applying a drop of each mixture to a smooth surface, drying the drops for at least 24 hours, determining the extent of salt crystallization in a peripheral zone of the dried sample mixtures, classifying the presence of singly occurring crystals, crystal conglomerates or complete crystallization respectfully as indicative of a weak, moderate or severe lithogenesis condition, determining a salt composition for the crystals in the peripheral zone and a central zone of the dried sample mixtures and determining the compositions of the calculi forming salts in the urine sample through a comparative analysis of the salt compositions of the two zones of the dried sample mixtures.
 14. A method as claimed in claim 13 wherein said aqueous protein solution is an 8-12% aqueous albumin solution.
 15. A method as claimed in claim 14 wherein the X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 16. A method as claimed in claim 13 wherein the drying of said drops of the mixtures produced by mixing a urine sample with an aqueous protein solution is carried out at room temperature.
 17. A method as claimed in claim 16 wherein the X-ray spectrum microanalysis is used to determine the composition of crystalline formations.
 18. A method as claimed in claim 13 wherein X-ray spectrum microanalysis is used to determine the composition of crystalline formations. 